Clonal analysis of quail neural crest cells in vitro has shown that crest cells are pluripotent and able differentiate into adrenergic cells and into melanocytes in the absence of continuous heterotypic cell-cell interactions. Components of the extracellular matrix, enhance adrenergic differentiation, whereas conditioned medium from heart cell cultures promotes cholinergic differentiation. These signals which are apparently governing the choice of neurotransmitter synthesized by crest cell progeny will be further analyzed and characterized with regard to their role in the regulation of neural crest cell differentiation.